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Distinct roles for LTalpha3 and LTalpha1beta2 produced by B cells contribute to their multi-faceted impact on ileitis.
Randolph, Gwendalyn; Erlich, Emma; Czepielewski, Rafael; Field, Rachael; Dunning, Taylor; Saleh, Leila; Hoofnagle, Mark; Tumanov, Alexei; Guilak, Farshid; Brestoff, Jonathan.
Afiliación
  • Randolph G; Washington University in St. Louis.
  • Erlich E; Washington University School of Medicine.
  • Czepielewski R; Washington University School of Medicine.
  • Field R; Washington University School of Medicine.
  • Dunning T; Washington University School of Medicine.
  • Saleh L; Washington University School of Medicine.
  • Hoofnagle M; Washington University in Saint Louis.
  • Tumanov A; University of Texas San Antonio.
  • Guilak F; Washington University in St. Louis.
  • Brestoff J; Washington University School of Medicine in St. Louis.
Res Sq ; 2024 Feb 26.
Article en En | MEDLINE | ID: mdl-38464070
ABSTRACT
B lymphocytes may facilitate chronic inflammation through antibody production or secretion of cytokines, including lymphotoxin (LT)-a1b2 associated with development of lymphoid tissue. Tertiary lymphoid structures (TLS) characterize human and murine ileitis by suppressing outflow from the ileum. Here, we show that B cell-derived secretory IgA protected against ileal inflammation, whereas B cell-derived LTa guarded against ileitis-associated loss of body mass. We initially hypothesized this protection resulted from formation of TLS that suppressed lymphatic outflow and thereby restrained systemic spread of inflammatory signals, but B cell-selective deletion of LTb did not exacerbate weight loss, despite eliminating TLS. Instead, weight loss driven by the cachectic cytokine TNF was exacerbated when LTa3, another ligand for TNF receptors, was selectively neutralized. Thus, B cells' multi-faceted impact on ileitis includes generating secretory IgA, expressing LTa1b2 to drive formation of TLS, and producing LTa3 for protecting against weight loss in the presence of TNF.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos